Despite recent advances in cancer research, the development of cell-specific therapies for the treatment of malignancies remain elusive. The many and complex factors that enable malignant cells to undergo mutations, evade immune protection and promote angiogenesis to deliver nutrients to the rapidly growing cells complicate the development of targeted treatment modalities. Current therapies have multiple untoward side effects. For example, chemotherapy results in multiple painful and sometimes lethal side effects. Advances in biotechnology have promoted the development of targeted biologicals with fewer side effects.
Host cells have surface receptors that associate with ligands to signal and cause host cell activities. The epidermal growth factor receptor helps control cell growth and metastasis. Many tumor cells express higher numbers of epidermal growth factor receptors than normal cells. A new treatment designated IMC-225 was specifically designed to target and block epidermal growth factor receptors, thus preventing cell division and repair. Recently, trastuzumab, which is a HER-2-specific monoclonal antibody, has proven effective at treating metastatic breast cancers. This antibody blocks interactions on cancer cells that inhibit cell growth. HER-2, however, is only found on about 25 to 30 percent of breast cancer cells.
Chemokines are a superfamily of small, cytokine-like proteins that are resistant to hydrolysis, promote neovascularization or endothelial cell growth inhibition, induce cytoskeletal rearrangement, activate or inactivate lymphocytes, and mediate chemotaxis through interactions with G-protein coupled receptors. Chemokines can mediate the growth and migration of host cells that express their receptors.
Chemokine (C-C motif) ligand 25 (CCL25), also known as Thymus-Expressed Chemokine (TECK), is a small cytokine belonging to the CC chemokine family. CCL25 is chemotactic for thymocytes, macrophages, and dendritic cells. CCL25 elicits its effects by binding the chemokine receptors CCR9 and is believed to play a role in the development of T-cells. Human CCL25 is produced as a protein precursor containing 151 amino acids. The gene for CCL25 (scya25) is located on human chromosome 19.
Chemokine (C-C motif) receptor 9 (CCR9), also known as GPR 9-6, is very highly expressed in thymus (on both immature and mature T-cells) while low in lymph nodes and spleen. CCR9 is also abundant in the gut, with its expression associated with T cells of the intestine. To note, the chemokine binding protein D6 had previously been referred to as CCR9, but this molecule is a scavenger receptor not a true (signaling) chemokine receptor.